Chronic toxicity and oncogenicity studies of Macrodantin in Sprague-Dawley rats

Chronic toxicity and oncogenicity studies of nitrofurantoin formulated as Macrodantin have been undertaken. The doses ranged from 12 to 116 mg/kg body weight/day. At 116 mg/kg/day, female rats showed a decreased weight gain. In the high-dose groups in the chronic toxicity study (males, 81 mg/kg/day; females, 116 mg/kg/day) there was an increase in testicular degeneration, sciatic nerve degeneration and fibrosis in both males and females, and an increase in focal biliary proliferation in females. There was no evidence of renal toxicity. There was no compound-related effect upon neoplasms at any site. In the oncogenicity study, an increase in focal biliary proliferation was observed in females given 31 or 56 mg/kg/day. There was no treatment-related increase in the incidence of neoplasms at any site. In particular there was no increase in the incidence of mammary or renal tumours. The observations in these studies indicate that therapeutic uses of Macrodantin would not present a carcinogenic hazard to man.